SUMMARY: C. albicans, a fungal gut commensal and opportunistic pathogen, causes 10% of all nosocomial bloodstream infections, >40% of which lead to death. The mammalian gut, a niche that harbors ~100 trillion microbes competing for nutrients, is a reservoir of C. albicans for dispersal and infection. Glucose is the preferred energy source for host cells and microbes, which both have sophisticated glucose sensing mechanisms. I will characterize a critical glucose-sensing pathway in C. albicans and determine its role in host colonization, virulence, and molecularly define C. albicans interactions with a major human gut symbiotic bacterium, B. theta. AIM 1: characterize the C. albicans glucose-sensing pathway by molecular techniques and in vitro assays. AIM 2: analyze colonization of the mammalian gut by C. albicans, and define the interactions between this fungus and a defined model human microbiota. AIM 3: assess the role of glucose sensing in virulence with a mouse model of disseminated Candidiasis. Long-term goals are to establish a model for C. albicans colonization of the human Gl tract, and use it to study C. albicans nutrient sensing and metabolism and its interactions with other organisms in a physiologically relevant niche. This work will form the foundation for future investigation of host-fungus interactions to explore how C. albicans colonizes immune compromised hosts. Career goals are to develop a comprehensive, independent research program. I have excellent training in genetics, mycology, functional genomics, host-fungus interactions, and mouse models of human disease. At the Washington University Center for Genome Sciences, I am surrounded by yeast geneticists, computational scientists, and microbiologists with one of the few existing gnotobiotic (germ-free) mouse facilities. Collaborations between these investigators merge gastroenterology, microbiology, fungal pathogenesis, yeast genetics, and functional genomics to create an environment to foster my independence. RELEVANCE: From birth to death, C. albicans causes most human yeast infections. It is important to understand how the fungus thrives in the gut of healthy individuals and how it causes disease, because this may offer ways to suppress it.